Beliefs and Attitudes of Health Care Professionals Toward Mental Health Services Users' Rights: A Cross-Sectional Study from the United Arab Emirates.

Purpose: The beliefs and attitudes of healthcare professionals (HCPs) towards service user's rights in mental healthcare are critical to understanding as it impacts the quality of care and treatment, leading to social discrimination and possible coercive professional practices. This study aimed to investigate the association between the HCPs' beliefs and attitudes towards service users' rights in seeking treatment in the UAE and to identify or may predict the stigmatized attitudes and behaviors among HCPs. Patients and Methods: Data was collected from HCPs participants working at three healthcare entities (n=307) allocated at selected primary and tertiary healthcare settings that specifically treat mental disorders. The Health Professionals Beliefs and Attitudes towards Mental Health Users' Rights Scale (BAMHS) questionnaire was used to assess the beliefs and attitudes. Unconditional associations using regression models included whether HCPs provide care to specific mental health patients, whether treating mental health patients is part of their jobs, whether HCPs receive professional training for mental healthcare, nationality of HCPs, and the number of years of professional experience. Results: Our findings demonstrate that HPCs understand mental disorders and feel that individuals' rights should be equal to those who do not have mental disorders while believing in autonomy and freedom, but there is a level of discrimination and a high level of social distance. HCPs are less tolerant when interacting with those with mental disorders outside their professional lives. Conclusion: Interventions with long-term follow-up activities must be implemented and assessed using assessment systems that measure acquired knowledge and actual behavioral change to ensure anti-stigma impact in practice and policy.

Stroke clot retrieval from Taranaki, New Zealand: a real-world regional experience.

AIM: Stroke clot retrieval (SCR) is now considered a standard of care for select stroke patients with proximal large vessel occlusion (LVO) of the anterior circulation. Here we present the experience of regional Taranaki patients transferred by air for SCR and compare this to metropolitan Auckland patients who were transferred by road. The aim is to present and compare process metrics and outcomes between the regional and metropolitan centres. METHODS: This is a retrospective analysis of consecutive patients with anterior LVO transferred to Auckland City Hospital (ACH) for SCR from Taranaki, Waitemata and Counties Manukau district health boards (DHBs) between November 2017 and December 2020. RESULTS: Thirty Taranaki patients were transferred for SCR, compared to 244 patients from Waitemata and Counties Manukau DHBs. Taranaki patients were seven years older and less ethnically diverse but similar in other characteristics. The proportion of patients with an independent Modified Rankin Scale (mRS) score between 0 and 2 at three months was the same as for the regional and metropolitan centres. CONCLUSIONS: In this real-world study, regional stroke patients can achieve similar SCR outcomes to metropolitan patients. Overcoming the post-code lottery for hyperacute stroke care can be achieved in a New Zealand setting.

HSF1 induces RNA polymerase II synthesis of ribosomal RNA in S. cerevisiae during nitrogen deprivation.

The resource intensive process of accurate ribosome synthesis is essential for cell viability in all organisms. Ribosome synthesis regulation centers on RNA polymerase I (pol I) transcription of a 35S rRNA precursor that is processed into the mature 18S, 5.8S and 25S rRNAs. During nutrient deprivation or stress, pol I synthesis of rRNA is dramatically reduced. Conversely, chronic stress such as mitochondrial dysfunction induces RNA polymerase II (pol II) to transcribe functional rRNA using an evolutionarily conserved cryptic pol II rDNA promoter suggesting a universal phenomenon. However, this polymerase switches and its role in regulation of rRNA synthesis remain unclear. In this paper, we demonstrate that extended nitrogen deprivation induces the polymerase switch via components of the environmental stress response. We further show that the switch is repressed by Sch9 and activated by the stress kinase Rim15. Like stress-induced genes, the switch requires not only pol II transcription machinery, including the mediator, but also requires the HDAC, Rpd3 and stress transcription factor Hsf1. The current work shows that the constitutive allele, Hsf1PO4* displays elevated levels of induction in non-stress conditions while binding to a conserved site in the pol II rDNA promoter upstream of the pol I promoter. Whether the polymerase switch serves to provide rRNA when pol I transcription is inhibited or fine-tunes pol I initiation via RNA interactions is yet to be determined. Identifying the underlying mechanism for this evolutionary conserved phenomenon will help understand the mechanism of pol II rRNA synthesis and its role in stress adaptation.

The role of age in the physiological adaptations and psychological responses in bikini-physique competitor contest preparation: a case series.

The increased popularity of the bikini-physique competitions has not translated to greater research identifying the influence of age on adaptations during contest preparation. The purpose of this case series was to observe how age may influence the adaptations normally seen during preparation and the exploration of newer protocols to address adaptations more relative to the judging standards. Over a 16-week pre-contest preparation, a 32-y bikini competitor (BC) and 44-y master's bikini competitor (MBC) visited the laboratory bi-weekly to observe changes in body fat mass (BF), lean body mass (LBM), bone mineral density (BMD), total body water (TBW); exploratory measures of deltoid cross-sectional area (DeltCSA), gluteus maximus muscle thickness (GMMT), and subcutaneous adipose tissue thickness (SAT); reproductive hormones estradiol (E2), luteinizing hormone (LH), and energy balance hormones triiodothyronine (T3), leptin and ghrelin; hydration status during contest preparation and the week of competition; resting metabolic rate (RMR); psychometric data related to perceived anxiety, stress, and body image were assessed. No differences between BC and MBC were observed in BF, LBM, BMD, and TBW. Both competitors showed a small loss in LBM. Both BC and MBC showed a contrasting increase in DeltCSA and a loss in GMMT. MBC showed to be slightly more dehydrated (1.025 vs 1.021 g·mL- 1) than BC. Both competitors maintained a euhydration status the day of the competition. No time differences were found between BC and MBC during RMR. BC showed a higher mean difference RMR compared to MBC (2.66 ± 0.75 kcal·kgLBM- 1·d- 1). MBC showed a higher mean difference in LH concentration (84.6 ± 6.01 IU·L- 1), which may be explained by perimenopausal status. MBC had a higher mean difference concentration of leptin (2.51 ± 0.24 ng·mL- 1·kgFM- 1), which was unperturbed by fat loss may be interrelated LH. BC self-reported a higher mean energy intake (15.07 ± 3.43 kcal·kgLBM- 1·d- 1) and higher aerobic training volume (93.26 ± 40.68 min·d). BC and MBC showed similar composition changes, slightly differing metabolic rates, and differing hormonal LH and leptin responses. This finding is in contrast to previous work showing both LH inhibition and leptin diurnal disturbance in younger, female athletes with low energy availability. The exploratory measures may have some benefit for bikini-physique competitors related to the judging criteria. Age did not seem to play a role in contest preparation adaptations.

Aesthetic presence: The role of the arts in the education of creative arts therapists in the classroom and online.

Literature about the integral role of the arts in learning is widely available, but much less has been written about how the arts and aesthetics support education in the creative arts therapies, particularly in the online learning environment. This article introduces the concept of aesthetic presence within the Community of Inquiry pedagogical model in line with values espoused within a Universal Design for Learning framework. The authors contextualize this concept with examples of how attention to the use of aesthetic and multimedia strategies in the classroom and in the online learning environment may foster openness and connection, encourage flexibility, humor, critical thinking, and animate and facilitate conversations about emergent and emotionally difficult themes while increasing accessibility for different kinds of learners.

Structure-guided discovery of a novel, potent, and orally bioavailable 3,5-dimethylisoxazole aryl-benzimidazole BET bromodomain inhibitor.

The bromodomain and extra-terminal (BET) family of proteins, consisting of the bromodomains containing protein 2 (BRD2), BRD3, BRD4, and the testis-specific BRDT, are key epigenetic regulators of gene transcription and has emerged as an attractive target for anticancer therapy. Herein, we describe the discovery of a novel potent BET bromodomain inhibitor, using a systematic structure-based approach focused on improving potency, metabolic stability, and permeability. The optimized dimethylisoxazole aryl-benzimidazole inhibitor exhibited high potency towards BRD4 and related BET proteins in biochemical and cell-based assays and inhibited tumor growth in two proof-of-concept preclinical animal models.

Genetic Mutations in the S-loop of Human Glutathione Synthetase: Links Between Substrate Binding, Active Site Structure and Allostery.

The second step in the biosynthesis of the cellular antioxidant glutathione (GSH) is catalyzed by human glutathione synthetase (hGS), a negatively cooperative homodimer. Patients with mutations in hGS have been reported to exhibit a range of symptoms from hemolytic anemia and metabolic acidosis to neurological disorders and premature death. Several patient mutations occur in the S-loop of hGS, a series of residues near the negatively cooperative γ-GC substrate binding site. Experimental point mutations and molecular dynamic simulations show the S-loop not only binds γ-GC through a salt bridge and multiple hydrogen bonds, but the residues also modulate allosteric communication in hGS. By elucidating the role of S-loop residues in active site structure, substrate binding, and allostery, the atomic level sequence of events that leads to the detrimental effects of hGS mutations in patients are more fully understood.

Metabolic health and academic achievement in youth at risk for high school dropout in rural Mississippi: The role of classroom management.

Disparities in health and academic achievement affect large cross-sections of the same population subgroups. This study examined the relationship metabolic health and academic achievement in youth "at risk" for school dropout in rural Mississippi. Fifteen adolescents participated in a studio based learning educational summer camp and subsequent follow-up sessions during the regular school year that were aimed at developing knowledge of core curriculum subjects by developing design projects based on the camp STEM-related theme. These projects are characteristic of a pedagogical technique known as Studio Based Learning (SBL) and involve more movement than a traditional classroom setting. Participants' metabolic health was assessed via measurements of blood lipids and glucose, blood pressure, BMI and waist circumference, and examined individually and as a combined risk score. Academic achievement measurements were obtained from district standardized testing. Mean BMI for this sample was classified as overweight; however, other metabolic parameters (blood lipids and glucose, and resting blood pressure) were in normal ranges for this age group. Little association was found between metabolic health and academic achievement and in this sample for math of language (r = -0.56 and 0.20, respectively). Participants took part in notable amounts of moderate-to-vigorous physical activity during the SBL camp and very little in the traditional classroom setting (approximately 30 vs. 7 min/day, respectively). Actively engaging teaching strategies, such as SBL, may impart a meaningful impact on physical activity levels of school-aged children, which may have long term, positive health outcomes.

Utility of whole-body (head-to-toe) PET/CT in the evaluation of melanoma and sarcoma patients.

OBJECTIVE: The aim of this study was to assess the added benefit of whole-body (head-to-toes) PET/CT versus routine 'eyes-to-thighs' PET/CT of melanoma and sarcoma patients. PATIENTS AND METHODS: We performed a retrospective review of consecutive whole-body PET/CT scans from January 2006 through December 2010 in patients with melanoma or sarcoma. PET abnormalities in the brain, distal thighs, and legs were recorded and clinical significance was assessed on the basis of pathology, imaging studies, and clinical follow-up. Patients with known primary lesions distal to the proximal femora were excluded as these patients would routinely undergo 'head-to-toe' PET/CT. RESULTS: We reviewed reports from 352 PET/CT examinations in 194 patients with melanoma and 75 PET/CT examinations in 44 patients with sarcoma. Melanoma: 13 patients had brain metastases on PET. In five of these patients, lesions were unknown, but all were in the setting of other metastatic disease. Twenty-seven patients had lower extremity metastases, all in the setting of other metastatic disease. No lower extremity metastases were found in the remaining 167 patients. Sarcoma: one patient had an isolated, unexpected brain metastasis. Six patients had leg metastases, but none were isolated. No lower extremity metastases were found in the remaining 38 patients. CONCLUSION: In patients with melanoma and sarcoma, inclusion of entire lower extremities adds little additional clinical value as detection of isolated, unexpected metastasis is rare. Brain imaging may add value as the presence of brain metastases alters clinical management. Overall, in patients with melanoma or sarcoma, whole-brain PET/CT imaging may be of value, but routine inclusion of the entire lower extremities adds little additional value.

Aerobic fitness impacts sympathoadrenal axis responses to concurrent challenges.

The combination of mental and physical challenges can elicit exacerbated cardiorespiratory (CR) and catecholamine responses above that of a single challenge alone. PURPOSE: This study examined the effects of a combination of acute mental challenges and physical stress on cardiorespiratory and catecholamine responses. METHOD: Eight below-average fitness (LF VO2max = 36.58 ± 3.36 ml-1 kg-1 min-1) and eight above-average fitness (HF VO2max = 51.18 ± 2.09 ml-1 kg-1 min-1) participants completed an exercise-alone condition (EAC) session consisting of moderate-intensity cycling at 60% VO2max for 37 min, and a dual-challenge condition (DCC) that included concurrent participation in mental challenges while cycling. RESULT: The DCC resulted in increases in perceived workload, CR, epinephrine, and norepinephrine responses overall. HF participants had greater absolute CR and catecholamine responses compared to LF participants and quicker HR recovery after the dual challenge. CONCLUSION: These findings demonstrate that cardiorespiratory fitness does impact the effect of concurrent stressors on CR and catecholamine responses.

Work duration does not affect cortisol output in experienced firefighters performing live burn drills.

Work duration may affect firefighters' stress responses. Forty-two firefighters (38 males) performed either 2 (SWD) or 3 (LWD) bouts of simulated fire suppression activity. Salivary cortisol, self-reported fear and anxiety, and perceptual thermal responses were measured. Cortisol was evaluated using area-under-the-curve calculations (Pruessner et al., 2003). Affective responses between the two conditions were compared using T-tests. Pearson product moment correlations were used to analyze the relationships between affect and change in thermal load perception. Cortisol decreased across the protocol in both groups, and no difference was found in cortisol or affect between the groups. Cortisol decreased (F4,36 = 3.43, p < 0.05) in the SWD group from a mean concentration of 40.93 ± 11.41 nmol/L to 25.07 ± 9.88 nmol/L at the end of the protocol. In the LWD group, the mean cortisol concentration decreased from 42.89 ± 11.83 to 25.07 ± 8.82 at the end of the protocol (F5,50 = 14.77, p < 0.01). Anxiety increased in the LWD (F4,72 = 5.11, p = 0.001) but not the SWD group. Fear increased in the SWD (F3,48 = 14.15, p < 0.001) and LWD group (F4,60 = 4.47, p < 0.01). The present findings suggests a moderate fear load with firefighting, which appears not to be associated with duration of work bout. Examination of more varied work bout lengths may reveal an association between anxiety and work duration. However, the work bout durations investigated in the current study comprise the range of what is practical from an occupational standpoint and the physiological capabilities of the firefighters.

Stress Markers During a Rally Car Competition.

The aim of the study was to assess the stress responses in drivers during an official rally car race and the influence of fitness and body composition on stress hormones. Fitness and body composition were assessed in 9 rally car drivers with an incremental exercise test for determination of maximum aerobic speed (MAS) and 6-site skinfold method, respectively. Before (pre) and after (post) the first stage of an official rally car race, data were collected for heart rate (HR), blood samples were collected for analysis of hormones (i.e., epinephrine [EPI], norepinephrine [NE], cortisol, and aldosterone) and metabolites (i.e., lactate [LA], glucose, and ammonia). There were significant (p ≤ 0.05) increases in all assessed variables except glucose at postrace. Heart rate increased 93% (p ≤ 0.05) at the end of the race stage, reaching 88.77 ± 4.96% of HRpeak. Also, EPI and NE significantly (p = 0.001) increased by 45 and 65%, respectively, and LA increased by 395% (p < 0.001). Significant correlations between percent body fat (%BF) and postrace EPI (r = 0.95; p < 0.001), and percentage change of EPI (r = 0.83; p = 0.012) were observed. The MAS was not associated to any metabolic or hormonal variable. These results suggest that psycho-physiological stress induced by the race elicited important changes in hormonal and metabolic variables and that %BF could be an important mediator of psycho-physiological stress in rally car drivers. Specific programs, including both strength and aerobic training, and nutritional plans should be implemented for appropriate conditioning of rally car drivers.

Incidence and Duration of Continuously Measured Oxygen Desaturation During Emergency Department Intubation.

STUDY OBJECTIVE: Desaturation during intubation has been associated with serious complications, including dysrhythmias, hemodynamic decompensation, hypoxic brain injury, and cardiac arrest. We seek to determine the incidence and duration of oxygen desaturation during emergency department (ED) rapid sequence intubation. METHODS: This study included adult rapid sequence intubation cases conducted between September 2011 and July 2012 in an urban, academic, Level I trauma center ED. We obtained continuous vital signs with BedMasterEX data acquisition software. Start and completion times of rapid sequence intubation originated from nursing records. We defined oxygen desaturation as (1) cases exhibiting SpO2 reduction to less than 90% if the starting SpO2 was greater than or equal to 90%, or (2) a further reduction in SpO2 in cases in which starting SpO2 was less than 90%. We used multivariable logistic regression to predict oxygen desaturation during rapid sequence intubation. RESULTS: During the study period, there were 265 rapid sequence intubation cases. The study excluded 99 cases for failure of electronic data acquisition, inadequate documentation, or poor SpO2 waveform during rapid sequence intubation, and excluded cases managed by anesthesia providers, leaving 166 patients in the analysis. After preoxygenation, starting SpO2 was greater than 93% in 124 of 166 cases (75%) and SpO2 was less than 93% in the remaining 46 cases. Oxygen desaturation occurred in 59 patients (35.5%). The median duration of desaturation was 80 seconds (interquartile range 40, 155). Multivariable analysis demonstrated that oxygen desaturation was associated with preintubation SpO2 less than 93% (odds ratio [OR] 5.1; 95% confidence interval (CI) 2.3 to 11.0), multiple intubation attempts (>1 attempt) (OR 3.4; 95% CI 1.4 to 6.1), and rapid sequence intubation duration greater than 3 minutes (OR 2.7; 95% CI 1.2 to 6.1). CONCLUSION: In this series, 1 in 3 patients undergoing ED rapid sequence intubation experienced oxygen desaturation for a median duration of 80 seconds. Preintubation saturation less than 93%, multiple intubation attempts, and prolonged intubation time are independently associated with oxygen desaturation. Clinicians should use strategies to prevent oxygen desaturation during ED rapid sequence intubation.

Mitotic Activation of a Novel Histone Deacetylase 3-Linker Histone H1.3 Protein Complex by Protein Kinase CK2.

Histone deacetylase 3 (HDAC3) and linker histone H1 are involved in both chromatin compaction and the regulation of mitotic progression. However, the mechanisms by which HDAC3 and H1 regulate mitosis and the factors controlling HDAC3 and H1 activity during mitosis are unclear. Furthermore, as of now, no association between class I, II, or IV (non-sirtuin) HDACs and linker histones has been reported. Here we describe a novel HDAC3-H1.3 complex containing silencing mediator of retinoic acid and thyroid hormone receptor (SMRT) and nuclear receptor corepressor 1 (N-CoR) that accumulated in synchronized HeLa cells in late G2 phase and mitosis. Nonetheless, the deacetylation activity by HDAC3 in the complex was evident only in mitotic complexes. HDAC3 associated with H1.3 was highly phosphorylated on Ser-424 only during mitosis. Isolation of inactive HDAC3-H1.3 complexes from late G2 phase cells, and phosphorylation of HDAC3 in the complexes at serine 424 by protein kinase CK2 (also known as casein kinase 2) activated the HDAC3 in vitro. In vivo, CK2α and CK2α' double knockdown cells demonstrated a significant decrease in HDAC3 Ser-424 phosphorylation during mitosis. HDAC3 and H1.3 co-localized in between the chromosomes, with polar microtubules and spindle poles during metaphase through telophase, and partially co-localized with chromatin during prophase and interphase. H1 has been reported previously to associate with microtubules and, therefore, could potentially function in targeting HDAC3 to the microtubules. We suggest that phosphorylation of HDAC3 in the complex by CK2 during mitosis activates the complex for a dual role: compaction of the mitotic chromatin and regulation of polar microtubules dynamic instability.

Obesity-Related Oxidative Stress: the Impact of Physical Activity and Diet Manipulation.

Obesity-related oxidative stress, the imbalance between pro-oxidants and antioxidants (e.g., nitric oxide), has been linked to metabolic and cardiovascular disease, including endothelial dysfunction and atherosclerosis. Reactive oxygen species (ROS) are essential for physiological functions including gene expression, cellular growth, infection defense, and modulating endothelial function. However, elevated ROS and/or diminished antioxidant capacity leading to oxidative stress can lead to dysfunction. Physical activity also results in an acute state of oxidative stress. However, it is likely that chronic physical activity provides a stimulus for favorable oxidative adaptations and enhanced physiological performance and physical health, although distinct responses between aerobic and anaerobic activities warrant further investigation. Studies support the benefits of dietary modification as well as exercise interventions in alleviating oxidative stress susceptibility. Since obese individuals tend to demonstrate elevated markers of oxidative stress, the implications for this population are significant. Therefore, in this review our aim is to discuss (i) the role of oxidative stress and inflammation as associated with obesity-related diseases, (ii) the potential concerns and benefits of exercise-mediated oxidative stress, and (iii) the advantageous role of dietary modification, including acute or chronic caloric restriction and vitamin D supplementation.

An intrinsically disordered region of methyl-CpG binding domain protein 2 (MBD2) recruits the histone deacetylase core of the NuRD complex.

The MBD2-NuRD (Nucleosome Remodeling and Deacetylase) complex is an epigenetic reader of DNA methylation that regulates genes involved in normal development and neoplastic diseases. To delineate the architecture and functional interactions of the MBD2-NuRD complex, we previously solved the structures of MBD2 bound to methylated DNA and a coiled-coil interaction between MBD2 and p66α that recruits the CHD4 nucleosome remodeling protein to the complex. The work presented here identifies novel structural and functional features of a previously uncharacterized domain of MBD2 (MBD2IDR). Biophysical analyses show that the MBD2IDR is an intrinsically disordered region (IDR). However, despite this inherent disorder, MBD2IDR increases the overall binding affinity of MBD2 for methylated DNA. MBD2IDR also recruits the histone deacetylase core components (RbAp48, HDAC2 and MTA2) of NuRD through a critical contact region requiring two contiguous amino acid residues, Arg(286) and Leu(287). Mutating these residues abrogates interaction of MBD2 with the histone deacetylase core and impairs the ability of MBD2 to repress the methylated tumor suppressor gene PRSS8 in MDA-MB-435 breast cancer cells. These findings expand our knowledge of the multi-dimensional interactions of the MBD2-NuRD complex that govern its function.

Idelalisib, a selective inhibitor of phosphatidylinositol 3-kinase-δ, as therapy for previously treated indolent non-Hodgkin lymphoma.

Idelalisib (GS-1101, CAL-101), an oral inhibitor of phosphatidylinositol 3-kinase-δ, was evaluated in a phase I study in 64 patients with relapsed indolent non-Hodgkin lymphoma (iNHL). Patients had a median (range) age of 64 (32-91) years, 34 (53%) had bulky disease (≥1 lymph nodes ≥5 cm), and 37 (58%) had refractory disease. Patients had received a median (range) of 4 (1-10) prior therapies. Eight dose regimens of idelalisib were evaluated; idelalisib was taken once or twice daily continuously at doses ranging from 50 to 350 mg. After 48 weeks, patients still benefitting (n = 19; 30%) enrolled into an extension study. Adverse events (AEs) occurring in 20% or more patients (total%/grade ≥3%) included diarrhea (36/8), fatigue (36/3), nausea (25/3), rash (25/3), pyrexia (20/3), and chills (20/0). Laboratory abnormalities included neutropenia (44/23), anemia (31/5), thrombocytopenia (25/11), and serum transaminase elevations (48/25). Twelve (19%) patients discontinued therapy due to AEs. Idelalisib induced disease regression in 46/54 (85%) of evaluable patients achieving an overall response rate of 30/64 (47%), with 1 patient having a complete response (1.6%). Median duration of response was 18.4 months, median progression-free survival was 7.6 months. Idelalisib is well tolerated and active in heavily pretreated, relapsed/refractory patients with iNHL. These trials were registered at clinicaltrials.gov as NCT00710528 and NCT01090414.

Idelalisib, an inhibitor of phosphatidylinositol 3-kinase p110δ, for relapsed/refractory chronic lymphocytic leukemia.

In a phase 1 trial, idelalisib (GS-1101, CAL-101), a selective inhibitor of the lipid kinase PI3Kδ, was evaluated in 54 patients with relapsed/refractory chronic lymphocytic leukemia (CLL) with adverse characteristics including bulky lymphadenopathy (80%), extensive prior therapy (median 5 [range 2-14] prior regimens), treatment-refractory disease (70%), unmutated IGHV (91%), and del17p and/or TP53 mutations (24%). Patients were treated at 6 dose levels of oral idelalisib (range 50-350 mg once or twice daily) and remained on continuous therapy while deriving clinical benefit. Idelalisib-mediated inhibition of PI3Kδ led to abrogation of Akt phosphorylation in patient CLL cells and significantly reduced serum levels of CLL-related chemokines. The most commonly observed grade ≥3 adverse events were pneumonia (20%), neutropenic fever (11%), and diarrhea (6%). Idelalisib treatment resulted in nodal responses in 81% of patients. The overall response rate was 72%, with 39% of patients meeting the criteria for partial response per IWCLL 2008 and 33% meeting the recently updated criteria of PR with treatment-induced lymphocytosis.(1,2) The median progression-free survival for all patients was 15.8 months. This study demonstrates the clinical utility of inhibiting the PI3Kδ pathway with idelalisib. Our findings support the further development of idelalisib in patients with CLL. These trials were registered at clinicaltrials.gov as #NCT00710528 and #NCT01090414.

Cardiorespiratory fitness does not alter plasma pentraxin 3 and cortisol reactivity to acute psychological stress and exercise.

Pentraxin 3 (PTX3) has been recently identified as a biomarker of vascular inflammation in predicting cardiovascular events. The purpose of this study was to examine the effect of cardiorespiratory fitness on plasma PTX3 and cortisol responses to stress, utilizing a dual-stress model. Fourteen male subjects were classified into high-fit (HF) and low-fit (LF) groups and completed 2 counterbalanced experimental conditions. The exercise-alone condition (EAC) consisted of cycling at 60% maximal oxygen uptake for 37 min, while the dual-stress condition (DSC) included 20 min of a mental stress while cycling for 37 min. Plasma PTX3 revealed significant increases over time with a significant elevation at 37 min in both HF and LF groups in response to EAC and DSC. No difference in plasma PTX3 levels was observed between EAC and DSC. In addition, plasma cortisol revealed a significant condition by time interaction with greater levels during DSC at 37 min, whereas cardiorespiratory fitness level did not reveal different plasma cortisol responses in either the EAC or DSC. Aerobic exercise induces plasma PTX3 release, while additional acute mental stress, in a dual-stress condition, does not exacerbate or further modulate the PTX3 response. Furthermore, cardiorespiratory fitness may not affect the stress reactivity of plasma PTX3 to physical and combined physical and psychological stressors. Finally, the exacerbated cortisol responses to combined stress may provide the potential link to biological pathways that explain changes in physiological homeostasis that may be associated with an increase in the risk of cardiovascular disease.